Dihydropyridines, calcium channel

ACE inhibitors - AT antagonists - Alpha blockers - Beta blockers Isolated syslolic hypertension (older patienls) - Diuretics preferred (generally Thiazides) - Long-acting dihydropyridine calcium channel blocker... 

Patients with asymptomatic left ventricular systolic dysfunction and hypertension should be treated with P-blockers and ACE inhibitors. Those with heart failure secondary to left ventricular dysfunction and hypertension should be treated with drugs proven to also reduce the morbidity and mortality of heart failure, including P-blockers, ACE inhibitors, ARBs, aldosterone antagonists, and diuretics for symptom control as well as antihypertensive effect. In African-Americans with heart failure and left ventricular systolic dysfunction, combination therapy with nitrates and hydralazine not only affords a morbidity and mortality benefit, but may also be useful as antihypertensive therapy if needed.66 The dihydropyridine calcium channel blockers amlodipine or felodipine may also be used in patients with heart failure and left ventricular systolic dysfunction for uncontrolled blood pressure, although they have no effect on heart failure morbidity and mortality in these patients.49 For patients with heart failure and preserved ejection fraction, antihypertensive therapies that should be considered include P-blockers, ACE inhibitors, ARBs, calcium channel blockers (including nondihydropyridine agents), diuretics, and others as needed to control blood pressure.2,49... 

Treatment with nondihydropyridine calcium channel blockers (diltiazem and verapamil) may worsen HF and increase the risk of death in patients with advanced LV dysfunction due to their negative inotropic effects. Conversely, dihydropyridine calcium channel blockers, although negative inotropes in vitro, do not appear to decrease contractility in vivo. Amlodipine and felodipine are the two most extensively studied dihydropyridine calcium channel blockers for systolic H F.39 4() These two agents have not been shown to affect patient survival, either positively or negatively. As such, they are not routinely recommended as part of a standard HF regimen however, amlodipine and felodipine can safely be used... 

Dihydropyridine calcium channel blockers Dopamine Estrogen Ethanol... 

The nondihydropyridine calcium channel blockers have been shown to also decrease protein excretion in patients with diabetes,20 but the reduction in proteinuria appears to be related to the reductions in blood pressure. The maximal effect of nondihydropyridine calcium channel blockers on proteinuria is seen with a blood pressure reduction to less than 130/80 mm Hg and no additional benefit is seen with increased doses. Dihydropyridine calcium channel blockers, however, do not have the same effects on protein excretion, and may actually worsen protein excretion.17... 

Calcium channel blockers Monitor for cardiovascular effects similarly to (3 -blockers. If dihydropyridine calcium channel blockers are employed, assess for dependent edema. Consider withdrawal if GERD or constipation responds poorly to therapy. 

ACE inhibitors and angiotensin-receptor blockers (ARB) have definite benefits in patients with nephropathy and are believed to have renoprotective effects in most patients. Due to their ability to cause an initial bump in serum creatinine, these agents should be used cautiously when employed in combination with the calcineurin inhibitors. The dihydropyridine calcium channel blockers have demonstrated an ability to reverse the nephrotoxicity associated with cyclosporine and tacrolimus (Table 52-8). In general, antihypertensive therapy should focus on agents with proven benefit in reducing the progression of cardiovascular disease and should be chosen on a patient-specific basis.55 See Chapter 2 for further recommendations for treating HTN. 

Mason, R. R Campbell, S. F. Wang, S.-D. Herbette, L. G., Comparison of location and binding for the positively charged 1,4-dihydropyridine calcium channel antagonist amlopidine with uncharged drugs of this class in cardiac membranes, Molec. Pharmacol. 36, 634—640 (1989). 

Kostic, D. et al. (1995). Intestinal absorption, serum clearance, and interactions between lutein and beta-carotene when administered to human adults in separate or combined oral doses. Am. J. Clin. Nutr. 62 604—610. Kuo, S. M. et al. (2001). Dihydropyridine calcium channel blockers inhibit ascorbic acid accumulation in human intestinal Caco-2 cells. Life Sci. 68(15) 1751-1760. 

Most patients with ESRD require three or more antihypertensive agents to achieve target blood pressure. As with less advanced CKD (see Fig. 76-4), ACEIs, ARBs, and dihydropyridine calcium channel blockers are the preferred agents. 

Adalat is a proprietary preparation of nifedipine (a dihydropyridine calcium-channel blocker). 

Flagyl (metronidazole, antimicrobial agent) tablets are available in 200 mg and 400 mg strengths. Istin (amlodipine, a dihydropyridine calcium-channel blocker) is available as 5 mg and 10 mg tablets. Risperdal (risperidone. 

Amlodipine and nifedipine are dihydropyridine calcium-channel blockers. Amlodipine differs from nifedipine in that it has a longer duration of action and can therefore be given once daily, unlike nifedipine. Both are indicated in hypertension and angina and tend to cause ankle oedema that does not respond to diuretic therapy. Neither amlodipine nor nifedipine are available as spray formulations. 

This strategy of modification of a neutral molecule by addition of basic functionality was employed in the discovery of the dihydropyridine calcium channel blocker, amlodipine. The long plasma elimination half-life (35 h) of amlodipine (Figure 4.8) is due, in large part, to its basicity and resultant high volume of distribution [13]. 

Fig. 4.8 Structures of the dihydropyridine calcium channel blockers, nifedipine (neutral) and amlodipine (basic).

Hypersensitivity to the drug hypersensitivity to dihydropyridine calcium channel blockers (nisodipine) sick sinus syndrome or second- or third-degree AV block... 

Drugs that may be affected by indinavir include antiarrhythmics, clarithromycin, dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressant agents, phosphodiesterase type 5 inhibitors, pimozide, saquinavir, trazodone, cisapride, amiodarone, benzodiazepines, ergot alkaloids, fentanyl, rifamycins, ritonavir. 

Drugs that may be affected by delavirdine include the following Clarithromycin, indinavir, amprenavir, benzodiazepines, cisapride, dihydropyridine calcium channel blockers, ergot derivatives, quinidine, sildenafil, warfarin, saquinavir, and didanosine. 

Figure 11.1. Structures of dihydropyridine calcium channel blockers (CCBs) (7-19).

Dihydropyridine calcium-channel blockers preferred over verapamil and diltiazem in patients with sinus bradycardia, conduction disturbances, and for combination... 

Meyer EB, Tally PW, Anderson RE, et al Inhibition of electrically induced seizures by a dihydropyridine calcium channel blocker. Brain Res 384 180-183, 1986 Meyer HH, Gottlieb R Theory of narcosis, in Experimental Pharmacology as a Basis for Therapeutics, 2nd Edition. Translated by Henderson VE. Philadelphia, PA, JB Lippincott, 1926, pp 116-29... 

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